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PubMed1997

Treatment of considerations in patients with compartment syndrome and an inherited bleeding disorder.

In addition to consultation with an experienced hematologist, the following are recommendations regarding compartment syndrome in a patient with an inherited bleeding disorder. Von Willebrand's Disease. Humate-P (rich in von Willebrand factor) is the replacement therapy of choice for surgical procedures in patients with von Willebrand's disease. In general, in the perioperative period, factor VIII levels between 50% and 100% are ideal with a gradual tapering to maintain levels at 50% for approximately 2 weeks. Adjuncts to therapy are DDAVP and EACA. Hemophilia A. During the initial evaluation and with measurement of compartment pressures, factor VIII replacement to levels in the range of 40% to 60% of normal is appropriate replacement therapy. For fasciotomy, however, factor VIII levels greater than 50% to 100% are required. In patients who have developed antibodies to factor VIII, a number of options are available. With low titers of factor VIII inhibitor, higher doses of factor VIII may be successful in overriding the inhibitor. In patients with higher titers of inhibitor, activated factor VII or porcine factor VIII is recommended. Hemophilia B. Highly purified factor IX replacement aimed at keeping factor levels between 50% and 100% in the perioperative period, followed by maintenance at 50% for approximately 2 weeks, is optimal management. Treatment Algorithm: The Figure outlines an algorithm to aid in the diagnosis and treatment of compartment syndrome in the patient with an inherited bleeding disorder. In a suspected case of compartment syndrome due to a soft-tissue hemorrhage or injury, factor replacement as outlined above should be initiated. Unequivocal clinical findings in the normal patient usually would be an indication to proceed to fasciotomy without obtaining compartment pressures. In the patient with an inherited bleeding disorder, however, factor replacement and subsequent normalization of the clotting cascade may help lowe compartment pressures. Therefore, we advocate obtaining initial pressures even with clinical findings of an acute compartment syndrome. At our institution, we advocate using an automated handheld pressure monitor (Stryker, Ontario, Canada) or the needle injection technique as described by Whitesides et al. In interpreting the obtained pressures, we choose to use the guidelines as described by Heppenstall et al. Briefly, Heppenstall et al determined that the pressure threshold at which cellular damage occurred was related more closely to the difference between the mean arterial blood pressure and compartment pressure than with the absolute compartment pressure alone; this measurement is called delta P. If delta P is > 30 mm Hg, then one should continue factor replacements and perform serial clinical and pressure examinations. Pressures should be taken every hour for 2 hours total. If the patient worsens in either respect, then the physician should enter the other limb of the algorithm for delta P < 30 mm Hg. For the patient with a delta P < 30 mm Hg, the amount of time since onset of symptoms must be considered. Since the patient may improve with adequate factor replacement, a delta P < 30 mm Hg mercury does not dictate automatic fasciotomy. An adequate time trial of replacement therapy may be attempted. In patients whose pressures do not begin normalizing, we advocate proceeding to fasciotomy. Patients who begin to normalize pressures during a 2-hour trial can be followed with serial clinical and pressure examinations. Any worsening in either scenario is an indication for fasciotomy; otherwise, observation and factor replacement may be continued. After initial decompression, staples may be placed in both wound edges with an elastic vascular loop woven between the two edges in a "shoelace" pattern. Then while waiting for closure, the loops can be gradually tightened at the bedside. Definitive closure should be attempted around the fifth postoperative day. All closure techniques should be pre

Algorithms↗

PubMed2005

Acute compartment syndrome in lower extremity musculoskeletal trauma.

Acute compartment syndrome is a potentially devastating condition in which the pressure within an osseofascial compartment rises to a level that decreases the perfusion gradient across tissue capillary beds, leading to cellular anoxia, muscle ischemia, and death. A variety of injuries and medical conditions may initiate acute compartment syndrome, including fractures, contusions, bleeding disorders, burns, trauma, postischemic swelling, and gunshot wounds. Diagnosis is primarily clinical, supplemented by compartment pressure measurements. Certain anesthetic techniques, such as nerve blocks and other forms of regional and epidural anesthesia, reportedly contribute to a delay in diagnosis. Basic science data suggest that the ischemic threshold of normal muscle is reached when pressure within the compartment is elevated to 20 mm Hg below the diastolic pressure or 30 mm Hg below the mean arterial blood pressure. On diagnosis of impending or true compartment syndrome, immediate measures must be taken. Complete fasciotomy of all compartments involved is required to reliably normalize compartment pressures and restore perfusion to the affected tissues. Recognizing compartment syndromes requires having and maintaining a high index of suspicion, performing serial examinations in patients at risk, and carefully documenting changes over time.

Compartment Syndromes↗

PubMed1995

Acute exertional anterior compartment syndrome in an adolescent female.

Acute compartment syndromes usually occur as a complication of major trauma. While the chronic exertional anterior tibial compartment syndrome is well described in the sports medicine literature, reports of acute tibial compartment syndromes due to physical exertion, or repetitive microtrauma, are rare. The case of an adolescent female who developed an acute anterior compartment syndrome from running in a soccer game is described in this report. Failure to recognize the onset of an acute exertional compartment syndrome may lead to treatment delay and serious complications. Whereas the chronic exertional anterior compartment syndrome is characterized by pain that diminishes with the cessation of exercise, the onset of the acute exertional anterior compartment syndrome is heralded by pain that continues, or increases, after exercise has stopped. Compartment pressure measurement confirms the clinical diagnosis and helps guide treatment. True compartment syndromes require urgent fasciotomy.

Acute Disease↗

PubMed1997

Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures.

We used compartmented cultures to study the regulation of adult sensory neurite growth by neurotrophins. We examined the effects of the neurotrophins nerve growth factor (NGF), neurotrophin-3 (NT3), and BDNF on distal neurite elongation from adult rat dorsal root ganglion (DRG) neurons. Neurons were plated in the center compartments of three-chambered dishes in the absence of neurotrophin, and neurite extension into the distal (side) compartments containing NGF, BDNF, or NT3 was quantitated. Initial proximal neurite growth did not require any of the neurotrophins, while subsequent elongation into distal compartments required NGF. After neurites had extended into NGF-containing distal compartments, removal of NGF by treatment with anti-NGF resulted in the cessation of growth with minimal neurite retraction. In contrast to the effects of NGF, no distal neurite elongation was observed into compartments with BDNF or NT3. To examine possible additive influences, neurite extension into compartments containing BDNF plus NGF or NT3 plus NGF was quantitated. There was no increased neurite extension into NGF plus NT3 compartments, while the combination of BDNF plus NGF resulted in an inhibition of neurite extension compared with NGF alone. We then investigated whether the regrowth of neurites that had originally grown into NGF subsequent to in vitro axotomy still required NGF. The results demonstrated that unlike adult sensory nerve regeneration in vivo, the in vitro regrowth did require NGF, and neither BDNF nor NT3 was able to substitute for NGF. Since the initial growth from neurons after dissociation (which is also a regenerative response) did not require NGF, it would appear that neuritic growth and regrowth of adult DRG neurons in vitro includes both NGF-independent and NGF-dependent components. The compartmented culture system provides a unique model to further study aspects of this differential regulation of neurite growth.

Animals↗

PubMed2007

Relationship of complex spike synchrony bands and climbing fiber projection determined by reference to aldolase C compartments in crus IIa of the rat cerebellar cortex.

Synchronous complex spike (CS) activity occurs most often among cerebellar Purkinje cells located in a narrow longitudinal (parasagittal) strip of cortex (synchrony band). The relationship of the anatomical organization of the olivocerebellar projection to these synchrony bands has not been investigated in detail. Thus, we studied this relationship by using the aldolase C (zebrin II) expression pattern, another landmark for the cerebellar longitudinal organization, as a reference frame in rat crus IIa. Crus IIa consists of 10 aldolase C-positive and -negative longitudinal compartments. Aldolase C labeling after multiple-electrode recording of CSs indicated that in lateral crus IIa (compartments 5+ to 7+) synchrony bands were generally constrained to single compartments. In contrast, in medial crus IIa (compartments 4a- to 5a-) the synchrony within and across the compartments was much higher than in lateral crus IIa, resulting in wide synchrony bands covering multiple compartments. Retrograde labeling of olivary neurons by injections of biotinylated dextran amine into aldolase C compartments in crus IIa showed that compartments in medial crus IIa were all innervated by the caudal part of the medial accessory olive. On the other hand, each aldolase C compartment in the lateral crus IIa was innervated by a region in a different subnucleus in the rostral inferior olive. These regions in different subnuclei were located close to each other. These results suggest that CS synchrony bands reflect the olivocerebellar compartmental projection pattern and neuronal coupling within a particular olivary subnucleus, and that medial and lateral crus IIa may be functionally distinct.

Action Potentials↗

PubMed1993

Isolation of a temperature-sensitive variant Chinese hamster ovary cell line with a morphologically altered endocytic recycling compartment.

We have enriched a mutagenized population of Chinese hamster ovary (CHO) cells for those defective in endocytosis by selection for survival to treatment with transferrin (Tf)-ricin and Tf-diphtheria toxin conjugates. Surviving cells were screened with a fluorescently labeled Tf uptake assay to identify cells with morphologically aberrant endocytic phenotypes. One of the cell lines identified, B104-5, has a striking temperature-induced alteration in the morphology of its endocytic receptor recycling compartment. In parental cells the tightly clustered endocytic recycling compartment is located near the Golgi complex. In the mutant cells, following incubation at 40 degrees C, this compartment appears fragmented and widely dispersed. Surprisingly, this alteration in the morphology of the recycling compartment has no effect on the kinetics of Tf internationalization and recycling. The wild-type endocytic compartment is closely aligned with the microtubule-organizing center and the Golgi apparatus, and like the Golgi, its clustered appearance is dependent upon intact microtubules. Although the disruption of the B104-5 receptor recycling compartment morphology can be phenocopied in wild-type cells by microtubule depolymerizing drugs, the microtubule cytoskeleton in B104-5 cells appears normal in immunofluorescent staining. B104-5 cells, unlike the parental cells, do not proliferate at 40 degrees C. The mutation in B104-5 cells is recessive, as fusion with wild-type cells results in a reversion of the B104-5 phenotype. The finding that the morphology of the recycling compartment in CHO cells can be altered without affecting recycling of endocytosed Tf is consistent with the variety of recycling compartment morphologies observed among different cell lines. An interpretation of this result is that the lesion in B104-5 cells is in a gene that is involved in determining the endocytic compartment morphologies observed in different cell lines.

Animals↗

PubMed1997

Formation of cytomegalovirus DNA replication compartments defined by localization of viral proteins and DNA synthesis.

To characterize the formation of replication compartments in human cytomegalovirus-infected cells, and to determine the fate of newly synthesized DNA, we localized viral replication proteins and DNA synthesis at early and late times during infection. As expected, ppUL57 (single-stranded DNA binding protein) and ppUL44 (DNA polymerase processivity factor) both localized to replication compartments beginning at 48 hpi. BrdU was incorporated into viral DNA in these compartments that was found to mature into progeny virus based on our ability to chase the label into the cytoplasm and out of the cell over the ensuing 72-h period. Although the pattern of BrdU incorporation at early times (20 or 24 hpi) was punctate, and distinct from the replication compartment that formed later during infection, viral DNA synthesized at this time also matured into progeny virus during a chase. Interestingly, sites of ppUL57 localization did not overlap completely with sites of BrdU incorporation at early times. Products from the UL112-113 gene localized to subnuclear regions by 6 hpi, earlier than ppUL57. Between 12 and 24 hpi, both ppUL57 and ppUL44 joined UL112-113 gene products at sites that subsequently developed into replication compartments. When infection was carried out in the presence of phosphonoformate or ganciclovir, replication compartment formation was blocked. A viral mutant deficient in uracil DNA glycosidase, previously shown to exhibit a delay in the initial phase of DNA replication, also exhibited delayed formation of replication compartments. These results raise the possibility that subnuclear sites defined by UL112-113 localization orchestrate the assembly of the CMV replication compartment and implicate punctate sites of BrdU incorporation as sites of early viral DNA replication that precedes the formation of the replication compartment.

Cell Compartmentation↗

PubMed1992

The pelvic compartment syndrome.

In the pelvic region three major compartments (gluteus medius-minimus compartment, gluteus maximus compartment, and iliopsoas compartment) can be distinguished from the smaller compartment of the tensor fasciae latae muscle. Pelvic compartment syndromes are rare. A clear history of trauma is often lacking. Association with drug and alcohol abuse is common, as is the association with the widespread use of anticoagulant therapy. From 1982 to 1990 six patients with acute buttock compartment syndrome were treated in the Department of Trauma Surgery of Hannover Medical School. In five patients fasciotomy of the gluteal compartment was performed. Two patients with a compartment syndrome secondary to necrotizing fasciitis died of septic multiple organ failure. The mean follow-up of the four other patients was 29 months (7-48 months). Three of these four patients revealed a decrease of gluteal muscle volume. Ergometric tests showed a decrease in gluteal muscle force in all patients.

Adolescent↗

PubMed2006

Soft tissue vibrations within one soft tissue compartment.

The concept of muscle tuning suggests that vibrations of the soft tissue compartments of the leg initiated by impacts are minimized by muscular activity prior to heel-strike of heel-toe running. For the quantification of muscle tuning it has been assumed (1) that the soft tissue compartment acts as one lumped mass and (2) that vibration energy dissipation does occur within one muscle. The purpose of this study was to test these two assumptions. It was hypothesized that (H1) the movement of the soft tissue compartment is not homogeneous, (H2) the vibration frequencies for different muscles within one soft tissue compartment are different and (3) attenuation of vibration movement within one muscle does occur. Soft tissue vibrations were measured using accelerometers on four locations on the quadriceps soft tissue compartment during heel-toe running. There were differences in the peak soft tissue acceleration and time of peak acceleration between accelerometer locations. The dominant frequency was similar throughout the soft tissue compartment, however; there was an attenuation of high-frequency vibration energy between distal and proximal points overlying one muscle. This evidence suggests that accelerometer placement is important when quantifying the acceleration magnitude and timing of peak soft tissue compartment but not when estimating the resonant vibration characteristics of a soft tissue compartment. It also provides initial evidence to support the idea that vibration control through muscle tuning may be achieved through changes in energy dissipating properties within the soft tissue compartment.

Acceleration↗

PubMed2002

Developmental compartments and planar polarity in Drosophila.

BACKGROUND: Planar polarity refers to the asymmetry of a cell within the plane of the epithelium; for example, cells may form hairs that point in a posterior direction, or cilia may beat in one way. This property implies that cells have information about their orientation; we wish to understand the nature of this information. Relevant also is the body plan of insects, which, in the ectoderm and somatic mesoderm, consists of a chain of alternating anterior and posterior compartments - basic units of development with independent cell lineage and subject to independent genetic control. RESULTS: Using the abdomen of adult Drosophila, we have taken genes required for normal polarity and either removed the gene or constitutively expressed it in small clones of cells and observed the effects on polarity. Hitherto, all such studies of polarity genes have not found any difference of behavior between the different compartments. We report here that the three genes, four-jointed, dachsous, and fat, cause opposite effects in anterior and posterior compartments. For example, in anterior compartments, clones ectopically expressing four-jointed reverse the polarity of cells in front of the clone, while, in posterior compartments, they reverse behind the clone. These three genes have been reported by others to be functionally linked. CONCLUSIONS: This discovery impacts on models of how cells read polarity. At the heart of one class of models is the hypothesis that cell polarity is determined by the vector of a morphogen gradient. Here, we present evidence that cell polarity in the abdomen depends on at least two protein gradients (Fj and Ds), each of which is reflected at compartment borders. Consequently, these gradients have opposing slopes in the two compartments. Because all polarized structures made by abdominal cells point posteriorly, we surmise that cells in each compartment are programmed to interpret these protein gradients with opposite signs, pointing up the gradient in one compartment and down the gradient in the other.

Animals↗

PubMed2003

The properties of acidic compartments in developing schistosomula of Schistosoma mansoni.

A variety of fluorescent probes have been used to study the acidic compartments in cercariae and schistosomula of Schistosoma mansoni. Freshly transformed schistosomula treated with the LysoTracker Red dye specific for lysosomes showed large acid-containing compartments (0.5-10 microm in size). The uptake of the dye is an energy-dependent process that depends on the metabolic activity of schistosomula. The compartments were quantified individually with respect to area, quantity of fluorescence and the total number/schistosomulum. Under normal conditions these compartments were not found in untreated cercariae, but appeared in cercariae slightly damaged by poly-L-lysine. The formation of these compartments seemed to be related to the development of cercariae into schistosomula as the number of compartments and uptake of fluorescence increased with time after transformation. Also, the method of transformation as well as the in vitro incubation of the parasite affected the percentage area of compartments/schistosomulum. Acid phosphatase enzyme activity was assessed using an endogenous phosphatase probe. Living and fixed schistosomula displayed the presence of enzyme activity in compartments of the same size and distribution as the acid-rich compartments. This was confirmed by histochemical staining showing deposition of enzyme-generated lead at the sites of phosphatase activity. We suggest that the development of acidic compartments is important during the transformation process or as a consequence of damage.

Acid Phosphatase↗

PubMed1998

Physiologically relevant one-compartment pharmacokinetic models for skin. 1. Development of models.

Many studies have used pharmacokinetic (compartment) models for skin to predict or analyze absorption of chemicals through skin. In these studies, several different definitions of the rate constants were used. The purpose of this study was to develop a general procedure for relating compartment model rate constants to dermal absorption parameters, such as permeability and partition coefficients, and to assess whether different definitions of the rate constants produce different results. Rate constant expressions were developed by requiring a one-compartment model to match a one-membrane model at specific conditions. Because a membrane model contains more information than a compartment model, a compartment model cannot match the membrane model in all respects. Consequently, many compartment models (i.e., different definitions of the rate constants) can be developed which match the membrane model for different conditions. Using this procedure, 11 different compartment models were developed and compared to the membrane model for four different dermal absorption scenarios. The compartment model that most closely matches the membrane model depends on the specific exposure scenario and what is to be predicted. One of the new compartment models agrees reasonably well with the membrane model, for the cases considered.

Models, Biological↗

PubMed2006

Two-compartment sorption of phenanthrene on eight soils with various organic carbon contents.

Sorption characteristics of phenanthrene (PHE) were studied on eight soils with organic carbon contents spanning over an order of magnitude using phase distribution relationships (PDRs) at 1 h, 48 h, and 720 h contact times. A new algebraic method was employed to describe the sorption characteristics at different time intervals (between 1 h and 48 h, and 1 h and 720 h). It was found that nonlinearity increased with increasing contact time and sorption that occurred in the subsequent time interval following the initial 1 h exhibited stronger isotherm nonlinearity. Sorption coefficients were positively correlated with the organic carbon contents of the soils. Detailed sorption dynamics were also examined on these soils. A two-compartment, first-order model was used to describe the sorption dynamics. The rate constants of the two compartments differed 18-170 times, suggesting the dissimilar sorption behaviors of the mathematically separated compartments. These two compartments were labeled fast and slow sorption compartment according to the rate constants. Calculation showed that the fast compartment accounted for over 80% of the overall sorption at the initial 1 h, while the slow compartment predominated the total sorption in the following 47 h. By combining the discussion of PDRs and sorption dynamics, the contributions of the two compartments to linear and nonlinear sorption were differentiated. The slow sorption compartment made a major contribution to nonlinear sorption and possibly to sequestration of organic pollutants by these soils.

Adsorption↗

PubMed2005

Rab15 effector protein: a novel protein for receptor recycling from the endocytic recycling compartment.

Sorting endosomes and the endocytic recycling compartment are critical intracellular stores for the rapid recycling of internalized membrane receptors to the cell surface in multiple cell types. However, the molecular mechanisms distinguishing fast receptor recycling from sorting endosomes and slow receptor recycling from the endocytic recycling compartment remain poorly understood. We previously reported that Rab15 differentially regulates transferrin receptor trafficking through sorting endosomes and the endocytic recycling compartment, suggesting a role for distinct Rab15-effector interactions at these endocytic compartments. In this study, we identified the novel protein Rab15 effector protein (REP15) as a binding partner for Rab15-GTP. REP15 is compartment specific, colocalizing with Rab15 and Rab11 on the endocytic recycling compartment but not with Rab15, Rab4, or early endosome antigen 1 on sorting endosomes. REP15 interacts directly with Rab15-GTP but not with Rab5 or Rab11. Consistent with its localization, REP15 overexpression and small interfering RNA-mediated depletion inhibited transferrin receptor recycling from the endocytic recycling compartment, without affecting receptor entry into or recycling from sorting endosomes. Our data identify REP15 as a compartment-specific protein for receptor recycling from the endocytic recycling compartment, highlighting that the rapid and slow modes of transferrin receptor recycling are mechanistically distinct pathways.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Prediction of serum vancomycin concentrations using one-, two- and three-compartment models with implemented population pharmacokinetic parameters and with the Bayesian method.

Although previous studies have shown that vancomycin has a complicated pharmacokinetic profile requiring description using a two- or, better, three-compartment model, until recently predictions of serum vancomycin concentrations have been mainly based on one- or two-compartment models using computer software packages. In this study, we have predicted serum vancomycin concentrations in 59 patients using one-, two- and three-compartment models with implemented population pharmacokinetic parameters in the Abbott PKS program and by use of the Bayesian method. The percentage errors of predictions made using the one-compartment model were smaller when either the Bayesian method or implemented population pharmacokinetic parameters were used (medians of -8.61% and -9.49%, respectively). Predictions using the one-compartment model with the Bayesian method were less biased (median of -1.52 microgmL(-1). The best predictions were those made using the three-compartment model with the Bayesian method-they were most accurate (median of 3.40 microgmL(-1) and highly precise (median of 11.53 microg(2)mL(-1)). The results suggest that predictions made using the one-compartment model with implemented population pharmacokinetic parameters are preferable if no samples are available, otherwise predictions made using the three-compartment model with the Bayesian method are preferable. The results also supported our previous argument that the greater the number of compartments involved in individualization, the better the predictions obtained using the Bayesian method.

Adult↗

PubMed1979

Identification of different sodium compartments from smooth muscle cells, fibroblasts and endothelial cells, in arteries and tissue culture.

1. The (22)Na efflux curve from the rat tail artery, at 35 degrees C, can be analysed as the sum of three distinct components, from 0 to 90 min of washout. After an initial diffusional component the two late exponential components Be(-kBt) and Ce(-kCt) have the following values: B = 3.03 +/- 0.15 m-mole/kg wet wt. and C = 0.56 +/- 0.04; k(B) = 0.145 +/- 0.005 min(-1) and k(C) = 0.015 +/- 0.007.2. In order to identify the cellular origin of the different compartments we compared the (22)Na efflux curve from the rat tail artery with the curves obtained from whole rabbit aortal strips, rabbit aortal medial or adventitial strips; and primary cultures from rabbit aorta medial smooth muscle cells, cultures of a non-fusing muscle cell line (BC(3)H1), fibroblasts and endothelial cells.3. It is possible to identify under these experimental conditions the cellular compartments from which the different exponential components of the efflux from the whole arteries originate. Fibroblasts and endothelial cultures, as well as adventitial strips exchange (22)Na slowly with exponential constants resembling k(C). Their efflux rate constants are: fibroblast cultures 0.010 +/- 0.002 min(-1), endothelial cells 0.015 +/- 0.003 min(-1) and adventitia 0.019 +/- 0.007 min(-1). Smooth muscle cells are exclusively responsible for the intermediate component Be(-kBt), but they present also a slow component, indistinguishible from the slow exponential component from the other types of cells in the artery. The rate constants for muscle cells are: rabbit aortic media k(B) 0.25 +/- 0.09 min(-1) and k(C) = 0.013 +/- 0.004 min(-1); medial cultures k(B) = 0.202 +/- 0.005 min(-1) and k(C1) = 0.020 +/- 0.003 min(-1); and BC(3)H1 cell culture k(B) = 0.205 +/- 0.083 min(-1) and k(C) = 0.016 +/- 0.003 min(-1).4. The efflux from compartment B of smooth muscle cells is inhibited by ouabain and in the absence of extracellular K(+). The efflux from compartment C is inhibited only by ouabain but not by the suppression of extracellular K(+).5. We propose a distribution of Na(+) in smooth muscle cells in two intracellular compartments: (1) Na(+) freely dissolved in the sarcoplasm, exchanging with the kinetics of compartment B and (2) a second cellular compartment which could be contained in the sarcoplasmic reticulum exchanging with the kinetics of compartment C.6. On the basis of the previous model of Na(+) distribution, considering our values, and without any correction, the estimated sarcoplasmic concentration of Na(+) is 9.6 mM, compatible with the direct measurements obtained in skeletal and heart muscle. The Na(+) concentration in the sarcoplasmic reticulum would be 4-10 times higher than in the cytoplasm. In order to increase the accuracy of our calculations it would be necessary to account for the interdiffusion and back diffusion of Na(+) between compartments. It is not possible to attain this goal at the present time.

Animals↗

PubMed1999

Differential patterns of altered bone formation in different bone compartments in established osteoporosis.

AIM: To investigate the level of bone formation in the different bone compartments in cases of established osteoporosis, as previous work has concentrated on trabecular bone alone. METHODS: Bone formation rates were measured histomorphometrically, in the periosteal (P), cortical (C), subcortical (SC), and trabecular (T) compartments in iliac crest biopsies from 159 patients with established osteoporosis. The values were standardised using age and sex matched control data and patterns of differential change determined by analysis of parametric status (increased, normal, reduced). RESULTS: Mean bone formation was reduced in all four compartments. This was more marked (4.4/4.1 standard deviations below the mean in C/T, v 2.3/0.9 in P/SC) and more frequent (reduced in 81.5%/78.3% in T/C, v 43.3%/44% in P/SC) in the trabecular and cortical compartments than in the periosteal or subcortical bone. Parametric status was equal in trabecular and cortical bone in 85.4% of cases, and in periosteal and subcortical bone in 65.7%, but in all four compartments in only 35.1%, indicating differential alteration of bone formation in the two sets of compartments (T/C v P/SC). CONCLUSIONS: Altered trabecular bone formation is important in osteoporosis, but there are differential patterns of alteration in the other three compartments, emphasising the presence of different microenvironments in bone; thus the effect on the cortical compartment was similar to that on the trabecular, while the subcortical and periosteal compartments also showed linkage. The linkage between the two pairs was divergent, indicating different control of bone formation, with resultant different patterns of perturbation in osteoporosis.

Adult↗

PubMed1984

In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment.

Rabbit antithrombin III (AT), purified by heparin-agarose, was labeled with iodine-131 by either the glucose oxidase-lactoperoxidase or iodine monochloride techniques. When intravenously injected, the disappearance of the 131I-AT from plasma was characterized by rapid initial decreases, and three-exponential equations were required for best fit of the plasma disappearance curves. This rapid 131I-AT removal was not caused by denaturation, as shown by comparison with results obtained when 131I-AT was biologically screened (injected into a first rabbit, and then transferred 16 h later in whole plasma to a second for kinetic evaluation) before injection. Thus, the same rapid initial loss of plasma 131I-AT was observed with screened preparations, and the plasma fractional catabolic rates of 0.716 +/- 0.048 and 0.673 +/- 0.051 day-1 for unscreened and screened 131I-AT were not significantly different. These results support the hypothesis that a vascular-endothelial AT compartment is present in rabbit. The fractions of the total-body AT in the plasma, the vascular-endothelial and the extravascular compartments were 0.337 +/- 0.031, 0.178 +/- 0.056, and 0.485 +/- 0.069, respectively. Two three-compartment kinetic models are discussed. The first pictures AT as distributing independently between plasma and two other compartments, and the second sees AT as first passing to the vascular-endothelial compartment, and then directly into the extravascular compartment. The plasma 131I-AT kinetic data was consistent with both models, but the sizes of the vascular-endothelial compartments were best predicted by the second. If AT catabolism was assigned to the plasma, both models generally underpredicted the whole-body radioactivities, while assignment of breakdown to the extravascular compartment generally resulted in overpredictions. This suggests that AT catabolism occurs from both plasma and extravascular compartments.

Animals↗